Angiogenesis, formation of new blood vessels from cells of preexisting vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis hold great promise in cancer treatment. We have proposed (and presented evidence in Phase I) that a specific recently characterized mammalian factor is an excellent candidate for a regulator of the initiation and progression of tumor angiogenesis. The specific aims of Phase II are: 1) the determination of whether blocking the angiogenic activity of this factor inhibits tumor growth and angiogenesis in vivo; 2) the use of this factor in the development of standardized ex vivo and in vivo assays to facilitate, respectively, large-scale screening and subsequent secondary small-scale screening to identify blockers of this factor as candidate anti-cancer agents; 3) the test-demonstration of this screening protocol to identify such candidate anti-cancer agents. Fulfillment of these aims would establish the validity and feasibility of developing this factor as a marketable reagent to discover novel anti-cancer agents, and also would identify potential anti-cancer agents that block the angiogenic activity of this factor. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of mortality in the U.S., and its health care costs are well over $100 billion. Solid tumors comprise the majority of cancers, afflict over 3 million people, and cause over a half million deaths annually. The health care market for anti-angiogenesis anti-cancer agents is very significant because conventional chemotherapy selects for resistant cancer cells, and causes significant toxicity to normal tissue.